The inhibition of red cell sickling by the modification of hemoglobin S with cyanate offers a promising treatment for patients with sickle cell anemia. Preliminary clinical trials of cyanate administration of extracorporeal carbamylation have noted a decrease in the hemolytic process as evidenced by increased red cell survival and red cell mass. Clinical and animal experiments have defined the upper limit of drug dosage as well as the side effects. The side effects of particular concern is a peripheral neuropathy that has been observed in several patients. Before cyanate can be more widely utilized and evaluated, it is important to define the nature of cyanate toxicity and if possible find ways to prevent it. The current renewal proposes to continue to assess the pharmacology of cyanate in experimental animals. The following are the goals of the study: 1. Study the effect of long-term administration of cyanate to monkeys, dogs, and rats. 2. Develop animal models to mimic the cyanate-induced peripheral neuropathy. 3. Study the effect of cyanate on nerve function and metabolism in vitro and in vivo. 4. Study the nature of the macromolecular component that is carbamylated in muscle, bone and nerve. It is hoped that these studies will further our understanding of the pharmacology of cyanate and allow its further development to occur.